Dlk1 expression relates to visceral fat expansion and insulin resistance in male and female rats with postnatal catch-up growth

Background: Although prenatal and postnatal programming of metabolic diseases in adulthood is well established, the mechanims underpinning metabolic programming are not. DLK1, a key regulator of fetal development, inhibits adipocyte differentiation and restricts fetal growth. Methods: Assess Dlk1 expression in Wistar rat model of catch-up growth following intrauterine restriction. Dams fed ad libitum deliverd control pups (C) and dams on a 50% calorie-restricted diet delivered pups with low birth weight (R). Restricted offspring fed a standard rat chow showd catch-up growth (R/C) but those kept on a calorie-restricted diet did not (R/R). Results: Decreased Dlk1 expression was observed in adipose tissue and skeletal muscle of R/C pups along with excessive visceral fat accumulation, decreased circulating adiponectin, increased triglycerides and HOMA-IR (from p<0.05 to p<0.001). Moreover, in R/C pups, the reduced Dlk1 expression in adipose tissue and skeletal muscle correlated with visceral fat (r= -0.820; p<0.0001) and HOMA-IR (r= -0.745; p=0.002). Conclusions: Decreased Dlk1 expression relates to visceral fat expansion and insulin resistance in a rat model of catch-up growth following prenatal growth restriction. Modulation of Dlk1 expression could be among the targets of the early prevention of fetal preogramming of adult metabolic disorders

Circulating fatty acid synthase in pregnant women: relationship to blood pressure, maternal metabolism and newborn parameters.

The enzyme FASN (fatty acid synthase) is potentially related with hypertension and metabolic dysfunction. FASN is highly expressed in the human placenta. We aimed to investigate the relationship circulating FASN has with blood pressure, maternal metabolism and newborn parameters in healthy pregnant women. Circulating FASN was assessed in 115 asymptomatic pregnant women in the second trimester of gestation along with C-peptide, fasting glucose and insulin, post-load glucose lipids, HMW-adiponectin and blood pressure (the latter was assessed in each trimester of gestation). At birth, newborns and placentas were weighed. FASN expression was also able to be assessed in 80 placentas. Higher circulating FASN was associated with lower systolic blood pressure (SBP), with a more favourable metabolic phenotype (lower fasting glucose and insulin, post load glucose, HbAc1, HOMA-IR and C-peptide), and with lower placental and birth weight (all p < 0.05 to p < 0.001). Placental FASN expression related positively to circulating FASN (p < 0.005) and negatively to placental weight (p < 0.05). Our observations suggest a physiological role of placental FASN in human pregnancy. Future studies will clarify whether circulating FASN of placental origin does actually regulate placental and fetal growth, and (thereby) has a favourable influence on the pregnant mother's insulin sensitivity and blood pressure

Serum alkaline phosphatase relates to cardiovascular risk markers in children with high calcium-phosphorus product

Although alkaline phosphatase (ALP) correlates with cardiovascular risk in adults, there are no studies in children. We evaluated the association between serum ALP levels, calcium-phosphorus product (Ca*P) and cardiovascular risk markers in healthy children. Children aged 7.9 ± 1.4 (n = 379) were recruited in this cross-sectional study. The main outcome measures were systolic and diastolic blood pressure (SBP and DBP) and carotid intima-media thickness (cIMT). Additional assessments were body-mass index (BMI), waist circumference, homeostatic model assessment of insulin resistance (HOMA-IR) and fasting lipids, ALP, serum calcium, phosphorus and Ca*P. ALP was directly correlated with BMI (p < 0.0001), waist circumference (p < 0.0001), SBP (p < 0.0001), cIMT (p = 0.005), HOMA-IR (p < 0.0001), and fasting triglycerides (p = 0.0001). Among them, in children with Ca*P values above the median the associations were BMI (r = 0.231; p = 0.001), waist (r = 0.252; p < 0.0001), SBP (r = 0.324; p < 0.0001), cIMT (r = 0.248; p = 0.001) and HOMA-IR (r = 0.291; p < 0.0001)]. ALP independently associated with SBP (β = 0.290, p < 0.001) and cIMT (β = 0.179, p = 0.013) in children with higher Ca*P, after adjusting for confounding variables. Circulating ALP is associated with a more adverse cardiovascular profile in children with higher Ca*P. We suggest that serum ALP and Ca*P levels could contribute to the assessment of risk for cardiovascular disease in children

Methylation of the C19MC microRNA locus in the placenta: association with maternal and chilhood body size.

OBJECTIVES: To study DNA methylation at the C19MC locus in the placenta and its association with (1) parental body size, (2) transmission of haplotypes for the C19MC rs55765443 SNP, and (3) offspring's body size and/or body composition at birth and in childhood. SUBJECTS AND METHODS: Seventy-two pregnant women-infant pairs and 63 fathers were included in the study. Weight and height of mothers, fathers and newborns were registered during pregnancy or at birth (n = 72). Placental DNA methylation at the C19MC imprinting control region (ICR) was quantified by bisulfite pyrosequencing. Genotyping of the SNP was performed using restriction fragment length polymorphisms. The children's body size and composition were reassessed at age 6 years (n = 32). RESULTS: Lower levels of placental C19MC methylation were associated with increased body size of mother, specifically with higher pregestational and predelivery weights and height of the mother (β from -0.294 to -0.371; R2 from 0.04 to 0.10 and all p < 0.019), and with higher weight, height, waist and hip circumferences, and fat mass of the child (β from -0.428 to -0.552; R2 from 0.33 to 0.56 and all p < 0.009). Parental transmission of the SNP did not correlate with an altered placental methylation status at the C19MC ICR. CONCLUSIONS: Increased maternal size is associated with reduced placental C19MC methylation, which, in turn, relate to larger body size of the child.This study was supported by grants from the Ministerio de Ciencia e Innovación, Instituto de 10 Salud Carlos III (ISCIII), Madrid, Spain (PI17/00557 to JB, and PI13/01257 and PI16/01335 to AL-B), projects co-funded by FEDER (Fondo Europeo de Desarrollo Regional). RF and MG acknowledge grant funding from the Fondation pour la Recherche Médicale (Equipes FRM, 13 grant number DEQ31703)

Renal size and cardiovascular risk in prepubertal children

Renal size is an important parameter for the evaluation and diagnosis of kidney disease and has been associated with several cardiovascular risk factors in patients with kidney failure. These results are however discordant and studies in healthy children are lacking. We aimed to study the association between renal size (length and volume) and cardiovascular risk parameters in healthy children. Clinical, analytical and ultrasound parameters [renal length, renal volume, perirenal fat and carotid intima-media thickness (cIMT)] were determined in 515 healthy prepubertal children (176 lean, 208 overweight and 131 obese). Renal length and volume associated significantly and positively with several anthropometric and cardiovascular risk parameters including cIMT and systolic blood pressure (SBP) (all p < 0.001). Renal length and volume associated with cIMT and SBP in all study subgroups, but these associations were predominant in obese children, in whom these associations were independent after adjusting for age, gender and BSA (all p < 0.05). In multivariate analyses in the study subjects as a whole, renal length was an independent predictor of cIMT (β = 0.310, p < 0.0001) and SBP (β = 0.116, p = 0.03). Renal size associates with cIMT and SBP, independent of other well-established cardiovascular risk factors, and may represent helpful parameters for the early assessment of cardiovascular risk in children

Integrated neuromuscular training intervention applied in schools induces a higher increase in salivary high molecular weight adiponectin and a more favorable body mass index, cardiorespiratory fitness and muscle strength in children as compared to the traditional physical education classes

BackgroundHigh-molecular-weight adiponectin (HMW-adiponectin) is a cardio-metabolic health protector. Objectives: (1) to compare body mass index (BMI), cardiorespiratory fitness (CRF) and muscle strength (MS) in healthy school-children depending on their baseline salivary-HMW-adiponectin concentration; and (2) to apply a 3-month integrated neuromuscular training (INT) and evaluate its effects on salivary-HMW-adiponectin concentration, BMI, CRF and MS in the same children. Additional goal: to identify if any potential changes during the 3-month period may be related to a potential change in salivary-HMW-adiponectin concentration.MethodsNinety children (7.4 ± 0.3 years) were recruited in primary schools and randomly allocated into control or intervention group. The intervention consisted of a 3-month INT applied during physical education (PE) classes, twice-weekly, while the control group had traditional PE classes. Body mass and height were measured, BMI was calculated and HMW-adiponectin was quantified in saliva. To assess CRF and MS, 800 m-run and hand-dynamometry were applied, respectively. All measurements were performed twice, at baseline and after 3 months.ResultsChildren with higher baseline salivary-HMW-adiponectin have more favorable BMI (p = 0.006) and slightly higher CRF (p = 0.017) in comparison to the children with lower baseline salivary-HMW-adiponectin. There were no big changes after the 3-month-period neither in the control, nor the INT group. However, it is worthy to note that the INT induced slightly higher increase in salivary-HMW-adiponectin (p = 0.007), and a slightly higher improvement in BMI (p = 0.028), CRF (p = 0.043) and MS (p = 0.003), as compared to the traditional PE classes. Finally, the INT-induced improvement in CRF was associated with the increased post-salivary-HMW-adiponectin concentration (p = 0.022).ConclusionMain findings may suggest the potential utility of an INT as a cost-effective strategy that can be applied in schools to induce cardio-protective effects in school-children

Salivary cardiac-enriched FHL2-interacting protein is associated with higher diastolic-to-systolic-blood pressure ratio, sedentary time and center of pressure displacement in healthy 7-9 years old school-children

IntroductionCardiac-enriched FHL2-interacting protein (CEFIP) is a recently identified protein, first found in the z-disc of striated muscles, and related to cardiovascular diseases. Our objectives are: 1) to quantify CEFIP in saliva in healthy 7-9 years old school-children; and 2) to assess the associations of salivary CEFIP concentration and blood pressure, physical (in)activity and physical fitness in these children.MethodsA total of 72 children (7.6 ± 0.3 years) were included in the study, recruited in primary schools in Girona (Spain). A sandwich enzyme-linked immunosorbent assay was used (abx506878; Abbexa, United Kingdom) to quantify CEFIP in saliva. Anthropometric evaluation was performed [body mass, height and body mass index (BMI)]. Systolic and diastolic blood pressure were measured by means of an electronic oscillometer and the diastolic-to-systolic blood pressure ratio (D/S BP ratio) was calculated. Physical (in)activity [sedentary time and time spent in physical activity (PA)] were assessed by means of a triaxial Actigraph GT3X accelerometer (Actigraph, Pensacola, FL, USA) that children were instructed to wear for 24h during 7 conssecutive days. Finally, physical fitness (speed and agility, explosive power of legs, handgrip strength, flexibility and balance) were assessed through validated and standardized testing batteries.ResultsCEFIP was easily detected and measured in all saliva samples (mean concentration: 0.6 ± 0.2 pg/ml). Salivary CEFIP was positively associated with D/S BP ratio (r=0.305, p=0.010) and sedentary time (r=0.317, p=0.012), but negatively associated with PA in 7-9 years old school-children (r=-0.350, p=0.002). Furthermore, salivary CEFIP was related to lower level of balance i.e., higher center of pressure (CoP) displacement in these children (r=0.411, p&lt;0.001). The associations of salivary CEFIP with D/S BP ratio (Beta=0.349, p=0.004), sedentary time (Beta=0.354, p=0.009) and CoP displacement (Beta=0.401, p=0.001), were maintained significant after adjustment for potential confounding variables such as age, gender and BMI in linear regression analyses.ConclusionCEFIP can be easily assessed in saliva as a promising biomarker associated with cardiovascular health in 7-9 years old school-children. Interestingly, higher salivary CEFIP concentration was related to higher D/S BP ratio, more sedentary time and higher CoP displacement i.e., lower level of balance in these children

Insulin resistance, C-reactive protein, diastolic to systolic blood pressure ratio and epicardial fat are related to sedentary time, and inversely related to physical activity in school-aged children

BackgroundPhysical activity (PA) is beneficial for the overall health. Objectives are: (1) To compare metabolic (MRM) and cardiovascular-risk-markers (CRM) in children according to their PA-level; (2) to explore the associations of MRM and CRM with PA and sedentary time (ST); and (3) to identify the associations between MRM and CRM in less (LA) and more active (MA) children.MethodsA total of 238 apparently healthy school-aged children were enrolled (132 boys/106 girls; 9.1 ± 1.8 years) and body mass index standard deviation score (BMI SDS) and blood pressure were assessed. Fasting venous blood sampling was performed to assess insulin resistance (HOMA-IR) and high-sensitivity-C-reactive protein (hsCRP). Epicardial fat, interventricular septal and left ventricular posterior wall thicknesses were assessed by high-resolution ultrasonography. PA and ST were assessed by enKid-questionnaire. Children were classified based on enKid-score as being LA and MA (below and above 50th percentile for PA).ResultsMA-children had lower values for: BMI SDS, diastolic-to-systolic blood pressure ratio, HOMA-IR and hsCRP (7.02 to 61.5% lower, p = 0.040 to p &lt; 0.0001) compared to LA-children. MRM and CRM were positively associated with ST (p = 0.003 to p &lt; 0.001), and negatively associated with PA (p = 0.044 to p &lt; 0.001). Finally, MRM were positively associated with CRM (p = 0.008 to p &lt; 0.0001). Interestingly, the latter associations were observed in LA-children but were not present in MA-children.ConclusionMore PA is associated with better cardio-metabolic profile in school-aged children. PA seems to modulate the associations between MRM and CRM, thus reinforcing the idea that fostering PA in children may lower the risk for development of a cardio-metabolic disease